An active area of research is in the discovery of P2Y12 antagonists. Different methods have been described for the synthesis of tetrahydro-furo[3,4][1,3]dioxole cores [D. Lipkin et al., Tetrahedron Lett., 1959, 21, 18-21; H. G. Korana et al., J. Am. Chem. Soc., 1962, 84(3), 430-440.; A. Hamilton et al., J. Am. Chem. Soc., 1965, 87(23), 5481; H. Wakuda, Nippon Kagaku Kaishi, Journal of the Chemical Society of Japan, Chemistry and Industrial Chemistry, 1998, 1, 40]. Although these methods appear to be general in scope, they do not adequately address the selective preparation of either cis or trans diastereomer, or to produce diastereomerically enriched products. In addition, these methods described in the literature are very time consuming (lasting over four days), and they sometimes involve the use of highly flammable solvents.
There is a need for a practical process for the preparation of a trans diastereomer of 4,6-disubstituted-tetrahydro-furo, thieno, pyrrolo and cyclopenta-[3,4][1,3]dioxoles.